Nevirapine not equivalent to EFV in Mozambicans with HIV and TB
A nevirapine-based antiretroviral regimen failed to attain noninferiority with an efavirenz (EFV) regimen in a randomized trial of Mozambican adults being treated for tuberculosis and starting their first antiretroviral combination.
Nevirapine and efavirenz are both widely prescribed in sub-Saharan Africa, where many regions have high rates of both HIV and TB. Both antiretrovirals interact with TB drugs, but they had not been compared in a randomized trial until this study.
The CARINEMO trial enrolled people 18 and older with tuberculosis and untreated HIV infection. Everyone had a CD4 count below 250 cells/μL and alanine aminotransferase and total bilirubin concentrations less than five times the upper limit of normal. All were in care at one of three centers in Maputo, Mozambique.
After 4 to 6 weeks of TB treatment, between October 2007 and March 2010, participants were randomized to full-dose nevirapine (200 mg twice daily) or efavirenz (600 mg once daily) plus stavudine and lamivudine. Median pretreatment CD4 count stood at 89 cells/μL. The primary endpoint was a viral load below 50 copies/mL in people who had received at least one antiretroviral dose (intention-to-treat analysis). The noninferiority margin for efficacy was set at 10%.
Of the 285 people enrolled into each treatment arm, 242 (85%) in the nevirapine group and 233 (82%) in the efavirenz group completed 48 weeks of follow-up. In the intention-to-treat population, 184 people assigned to nevirapine (64.6%, 95% confidence interval [CI] 58.7% to 70.1%) and 199 assigned to efavirenz (69.8%, 95% CI 64.1% to 75.1%) reached the primary endpoint of a sub-50-copy viral load at week 48. The difference between regimens, 11.7%, indicated that nevirapine was not noninferior to efavirenz.
In the per-protocol analysis, 170 of 242 people assigned to nevirapine (70.0%, 95% CI 63.8% to 75.7%) had a sub-50-copy load at week 48, compared with 194 of 246 assigned to efavirenz (78.9%, 95% CI 73.2% to 83.8%). The difference between arms was 15.4%.
Six people assigned to nevirapine switched to efavirenz, and 15 assigned to efavirenz switched to nevirapine. Equivalent proportions of participants (7% on nevirapine and 6% on efavirenz) had grade 3 to 4 increases in alanine aminotransferase. Three people assigned to nevirapine (1%) and none assigned to efavirenz had severe rash. Eighteen people in the nevirapine group and 17 in the efavirenz group died.
“Although non-inferiority of the nevirapine-regimen was not shown,” the researchers propose, “nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz.”
Source: Maryline Bonnet, Nilesh Bhatt, Elisabeth Baudin, Carlota Silva, Christophe Michon, Anne-Marie Taburet, Laura Ciaffi, Agnès Sobry, Rui Bastos, Elizabete Nunes, Christine Rouzioux, Ilesh Jani, Alexandra Calmy, for the CARINEMO study group. Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial. Lancet Infectious Diseases. Available online 20 February 2013.
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For more on the CARINEMO trial
Source: IAS
